Mannosidase, alpha, class 2a2 (MAN2A2)

Many proteins synthesized through the secretory pathway are posttranslationally modified by N-glycosylation. Alpha-mannosidase II (MAN2A1) and alpha-mannosidase IIx (MAN2A2) are key enzymes that convert precursor high mannose-type N-glycans to mature complex-type structures. While alpha-mannosidase II activity had been characterized by the time the mechanism of N-glycan processing was recognized (Kornfeld and Kornfeld 1985), investigators did not discover an alternative processing pathway until Man2a1 null mutant mice were generated and found capable of synthesizing complex-type N-glycans (Chui et al. 1997). Man2a2 then became a candidate for mediating that alternate pathway of N-glycan synthesis, but support for the pathway was lacking until creation of Man2a1/Man2a2 double knockout mice, which showed a complete loss in the ability to synthesize complex-type N-glycans (Fig. 117.1) (Akama et al. 2006).